title: Attenuation of thrombolysis-induced increase of plasminogen activator inhibitor-1 by intravenous enalaprilat.
abstract: We examined the effect of intravenous enalaprilat on the course of PAI-1 plasma levels in 23 patients with acute myocardial infarction undergoing thrombolytic therapy. All patients received 100 mg aspirin, 1000 IU/h heparin, thrombolysis with 100 mg rt-PA within 90 min, and betablockers. Eleven out of 23 patients received 5 mg enalaprilat intravenously prior to thrombolysis. Blood samples for determination of PAI-1 plasma levels were collected on admission, 2, 4, 6, 12, and 24 h after thrombolysis. PAI-1 plasma levels in patients receiving enalaprilat were similar to those of the control patients before thrombolysis (5 ng/ml, 95% confidence interval: 2-10 vs. 7 ng/ml, 95% confidence interval: 2-10; p = 0.5). The PAI-1AUC was 9 ng/ml/h (95% confidence interval: 5-10) in the enalaprilat group and 19 ng/ml/h (95% confidence interval: 13-26) in the control group (p = 0.0006). The maximum difference was observed 6 h after thrombolysis (enalaprilat: 13 ng/ml, 95% confidence interval: 5-25, control: 42 ng/ml, 95% confidence interval: 18-55; p = 0.003). Our study clearly demonstrates that application of intravenous enalaprilat prior to thrombolysis attenuates the thrombolysis-related increase of PAI-1. This finding may suggest a possible therapeutic approach to influence the fibrinolytic system in patients with acute myocardial infarction after thrombolysis.
authors.affiliation: Department of Emergency Medicine, University of Vienna, Austria.
authors.forename: M M
authors.initials: MM
authors.lastname: Hirschl
authors.forename: A
authors.initials: A
authors.lastname: Wagner
authors.forename: M
authors.initials: M
authors.lastname: Gwechenberger
authors.forename: H
authors.initials: H
authors.lastname: Herkner
authors.forename: M
authors.initials: M
authors.lastname: Müllner
authors.forename: C
authors.initials: C
authors.lastname: Woisetschläger
authors.forename: A N
authors.initials: AN
authors.lastname: Laggner
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D015773:Enalaprilat / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011446:Prospective Studies; D015912:Thrombolytic Therapy; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D017395:Plasminogen Activator Inhibitor 1; D015773:Enalaprilat